APPROACH

TO LIVER DISEASE

LIFE LOVES THE LIVER OF IT
- Maya Angelou

LIVER



WHO HAS A LIVER DISEASE?

FUNCTIONS OF THE LIVER:
SECRETORY:
o Bile acid form cholesterol
o Conjugation of bilirubin (Both secreted
in the bile)
EXCRETORY
o Excretion of exogenous dyes:
BSP
Rose Bengal
METABOLIC
o Carbohydrate metabolism
o Lipid metabolism
o Amino acid metabolism
o Cholesterol synthesis and esterification
o Ammonia formation
o Mineral metabolism
o Vitamin metabolism
o Nucleic acid metabolism
o Interconversion of sugars
SYNTHESIS
o Synthesis of:
Albumin
Alpha-1 and gamma 2 globulins
Clotting factors
Binding proteins
Transport proteins

DETOXIFICATION
o Xenobiotics
o Steroids
o Thyroid hormone
o Endogenous metabolites
STORAGE
o Glycogen
o B12
o Vitamin A

SUMMARY OF LIVER FUNCTION TESTS
SECRETORY FUNCTION BASED TESTS
Estimation of:
o Serum bilirubin
o Urinary bilirubin and urobilinogen
o Van den Bergh Reaction
EXCRETORY FUNCTION BASED TESTS
o BSP Retention Test
o I Rose Bengal dye test
METABOLISM BASED TESTS
o Carbohydrate metabolism
Galactose Tolerance Test
Fructose Tolerance Test
o Lipid Metabolism
Serum total cholesterol concentration
Esterified cholesterol concentration
Ratio of Free: Esterified Cholesterol
concentration
Faecal fat content estimation
o AMINO ACID METABOLISM
Blood NH3 level
CSF Glutamine level
SYNTHETIC FUNCTION BASED TESTS
Estimation of:
o Serum Total Albumin
o Differential Proteins
o A:G Ratio
o Serum Fibrinogen
o Prothrombin Time and Index
DETOXIFICATION FUNCTION BASED TEST
o Hippuric acid Excretion Test
o MEGX test
o Anti-pyrin Breath test
SERUM ENZYMES IN LIVER DISORDERS:
o ALT
o AST
o ALP
o GGT


o 5 Nucleotidase
o LDH

ALGORITHM FOR LIVER DISEASE

LIVER TEST
measures of hepatobiliary cell injury
measures of transport efficiency of organic
compounds
measures of hepatic synthetic function

TESTS REFLECTING CELL INJURY
Aminotransferases (ALT & AST)
Alkaline Phosphatases
Transpeptidases
5-Nucleotidase

o AMINOTRANSFERASES
ASPARTATE AMINOTRANSFERASE (AST)
in cytosol and mitochondria
liver > heart > skeletal muscle > kidneys >
brain > pancreas > lungs > WBCs > RBCs
ALANINE AMINOTRANSFERASE (ALT)
in cytosol
predominantly liver
more sensitive and specific than AST

O ALKALINE PHOSPHATASE
catalyzes organic phosphate esters
the enzyme is bound to hepatic canalicular
membrane
elevation may be due to induction of
enzyme synthesis rather than inability of
liver to secrete it into the bile
increases seen with cell injury or
obstruction
slight to moderate (1-2x) usually
hepatocellular
large increases (3-10x) obstruction or
cholestasis

O -GLUTAMYL TRANSPEPTIDASE (GGT)
catalyzes transfer of -glutamyl groups
high concentrations in bile ductule
epithelial cells
useful to exclude bone source for Alk Phos
correlates with alk phos levels in liver
disease
sensitive but not specific
in renal failure, MI, pancreatitis, diabetes

O 5-NUCLEOTIDASE (5NT)
hydrolyzes 5 phosphates from nucleotides

associated with canalicular and sinusoidal
membranes
physiologic function unknown
only hepatobiliary tissue can release 5-NT
specific for hepatic disease
highest in cholestatic conditions

TESTS MEASURING TRANSPORT EFFICIENCY
1. delivery to hepatocyte
2. uptake by hepatocyte
3. transport within hepatocyte
4. molecular alterations within hepatocyte
5. secretion into bile
6. passage down bile ducts


o acute liver failure
o dietary

TESTS MEASURING TRANSPORT EFFICIENCY

BILIRUBIN
- derived mainly from hemoglobin (95%)
- continuous production (300 mg daily)
- normal liver reserve can rev up 2-3 times
- normal values of total bilirubin = 0.1-1.0
mg/dL
o conjugated plus unconjugated
o direct plus indirect
- jaundice evident with levels >3.0 mg/dL

TESTS MEASURING SYNTHETIC FUNCTION

PROTHROMBIN TIME (PT)
- sick liver cant make clotting factors
o factors 2, 5, 7, 9, 10 (made only in the
liver)
- prolonged PT reflects failure of liver
synthesis
- Other causes of prolongation:
o congenital deficiencies
o consumptive coagulopathies (i.e., DIC)
o drugs (i.e., warfarin)
o vitamin K deficiency (i.e., dietary, bile
output)

ALBUMIN
- most important plasma protein made by the
liver
o accounts for 65% of protein in serum
o half-life ~17-21 days
- useful indicator of liver function
- Other causes of decrease:
o sepsis or multiple organ failure

LIVER BIOPSY
1. Hepatocellular disease of uncertain cause
2. Chronic active hepatitis
3. Unexplained Hepatomegaly
4. Unexplained Splenomegaly
5. Hepatic filling defects by radiologic imaging
6. Fever of unknown origin
7. Staging of Malignant Lymphoma


LIVER DISEASES
o VIRAL HEPATITIS
o CHOLECYSTITIS AND CHOLANGITIS
o ALCOHOLIC LIVER DISEASE
o NAFLD (NONALCOHOLIC FATTY LIVER)
o DRUG INDUCED (ACETAMINOPHEN)
o HCC; ABSCESS; CYST

**TABLE TAKEN FROM HARRISONS PRINCIPLES OF

INTERNAL MEDICINE, 18TH EDITION. CHAPTER 301.
APPROACH TO THE PATIENT WITH LIVER DISEASE, PAGE
2521 J